Guanine nucleotide exchange factors (“GEFs”) stimulate the dissociation of the GTP hydrolytic product, GDP, from small GTP-binding proteins, to promote the binding of a new GTP molecule. In doing so, this GEF-facilitated exchange of GDP for GTP is associated with structural changes in the GTP-binding protein which influence the degree to which the GTP-binding protein can interact with other molecules. When GTP is bound, for instance, Ras proteins can interact with effectors and other molecules to affect cell proliferation, differentiation and apoptosis.
The possible importance of GEFs in the spatial localization of changes in the actin cytoskeleton is beginning to be understood. See, Shamah et al., Cell, 20:105(2):233-44, 2001. From an evolutionary perspective this spatial control is satisfied in that the distant relative S. cerevisiae Cdc24, a GEF for Cdc42, plays a key role in targeting cytoskeletal changes to different spatial domains of the cell in response to different signals O'Shea et al., Nature Cell Biol., 2(3):E39-41, 2000.
Thus, existing techniques and current knowledge have not used nor addressed the interactions of GEF-H1 with other proteins as a means by which cell proliferation can be controlled or the detection and treatment of cancerous, tumorigenic cells and tissues be developed.